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Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia

Lookup NU author(s): Professor Raj Kalaria


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Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD. © 2005 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Roman GC, Kalaria RN

Publication type: Review

Publication status: Published

Journal: Neurobiology of Aging

Year: 2006

Volume: 27

Issue: 12

Pages: 1769-1785

ISSN (print): 0197-4580

ISSN (electronic): 1558-1497


DOI: 10.1016/j.neurobiolaging.2005.10.004